Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer's disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics

被引：1

作者：

Xu, Shuling ^{[1
]}

Zhu, Zhijun ^{[2
]}

Delafield, Daniel G. ^{[2
]}

Rigby, Michael J. ^{[3
,4
,5
]}

Lu, Gaoyuan ^{[1
]}

Braun, Megan ^{[3
,4
,5
]}

Puglielli, Luigi ^{[3
,4
,6
]}

Li, Lingjun ^{[1
,2
,7
,8
]}

机构：

[1] Univ Wisconsin Madison, Sch Pharm, Madison, WI 53705 USA

[2] Univ Wisconsin Madison, Dept Chem, Madison, WI 53706 USA

[3] Univ Wisconsin Madison, Dept Med, Madison, WI 53705 USA

[4] Univ Wisconsin Madison, Waisman Ctr, Madison, WI 53705 USA

[5] Univ Wisconsin, Neurosci Training Program, Madison, WI 53705 USA

[6] Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Madison, WI 53705 USA

[7] Univ Wisconsin Madison, Lachman Inst Pharmaceut Dev, Sch Pharm, Madison, WI 53705 USA

[8] Univ Wisconsin Madison, Wisconsin Ctr NanoBioSystems, Sch Pharm, Madison, WI 53705 USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

MASS-SPECTROMETRY; PHOSPHOLIPASE A(2); STRUCTURAL-CHARACTERIZATION; DOCOSAHEXAENOIC ACID; PREDICTION; ISOMERS; STRATEGIES; DIVERSITY; MEDIATORS; LIPIDS;

D O I：

10.1038/s41467-024-50299-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dysregulated glycerophospholipid (GP) metabolism in the brain is associated with the progression of neurodegenerative diseases including Alzheimer's disease (AD). Routine liquid chromatography-mass spectrometry (LC-MS)-based large-scale lipidomic methods often fail to elucidate subtle yet important structural features such as sn-position, hindering the precise interrogation of GP molecules. Leveraging high-resolution demultiplexing (HRdm) ion mobility spectrometry (IMS), we develop a four-dimensional (4D) lipidomic strategy to resolve GP sn-position isomers. We further construct a comprehensive experimental 4D GP database of 498 GPs identified from the mouse brain and an in-depth extended 4D library of 2500 GPs predicted by machine learning, enabling automated profiling of GPs with detailed acyl chain sn-position assignment. Analyzing three mouse brain regions (hippocampus, cerebellum, and cortex), we successfully identify a total of 592 GPs including 130 pairs of sn-position isomers. Further temporal GPs analysis in the three functional brain regions illustrates their metabolic alterations in AD progression.

引用

页数：18